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Publication Open Access Anti-pan-neurofascin IgG3 as a marker of fulminant autoimmune neuropathy(Lippincott Williams and Wilkins (LWW), 2019) Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)Objective: to identify and characterize patients with autoantibodies against different neurofascin (NF) isoforms. Methods: screening of a large cohort of patient sera for anti-NF autoantibodies by ELISA and further characterization by cell-based assays, epitope mapping, and complement binding assays. Results: two different clinical phenotypes became apparent in this study: The well-known clinical picture of subacute-onset severe sensorimotor neuropathy with tremor that is known to be associated with IgG4 autoantibodies against the paranodal isoform NF-155 was found in 2 patients. The second phenotype with a dramatic course of disease with tetraplegia and almost locked-in syndrome was associated with IgG3 autoantibodies against nodal and paranodal isoforms of NF in 3 patients. The epitope against which these autoantibodies were directed in this second phenotype was the common Ig domain found in all 3 NF isoforms. In contrast, anti-NF-155 IgG4 were directed against the NF-155-specific Fn3Fn4 domain. The description of a second phenotype of anti-NF-associated neuropathy is in line with some case reports of similar patients that were published in the last year. Conclusions: our results indicate that anti-pan-NF-associated neuropathy differs from anti-NF-155-associated neuropathy, and epitope and subclass play a major role in the pathogenesis and severity of anti-NF-associated neuropathy and should be determined to correctly classify patients, also in respect to possible differences in therapeutic response.Publication Open Access Antimuscarinic-induced convulsions in fasted rats after food intake: EEG patterns of fasting, scopolamine treatment, and convulsions(Galenos Yayınevi, 2022) Türkmen, Aslı Zengin; Nurten, Asiye; Edis, Bilge Özerman; Özen, İlknur; Kara, İhsan; Karamürsel, Sacit; Faculty Member; School of Medicine; 19597Objective: antimuscarinic treatment in fasted mice and rats causes clonic convulsion soon after food intake. This study was designed to evaluate the electrophysiological markers of these convulsions and fasting in electrocorticograms in rats. Methods: Male Wistar albino rats were stereotaxically implanted with 10 cortical electrodes, and baseline electroencephalogram recordings were taken for 10 minutes. After weighing, rats were deprived of food for 52 hours. At the 24th and 52nd hours of deprivation, continuous electroencephalogram recordings were repeated. After the deprivation period, animals were treated with saline or scopolamine (3 mg/kg). Twenty minutes after injections, animals were given food pellets. After eating food, electroencephalogram recordings were taken for 60 minutes and all animals were observed simultaneously to determine the incidence and onset of convulsions. Results: these results show that food deprivation for 52 hours decreased the amplitude of the gamma band when compared to basal (P <.05) and 24 hours (P <.008) food deprivation. And the amplitude of the beta band in the 52nd hour decreased when compared to the 24th hour of food deprivation (P <.05). The treatment with scopolamine changes the effects of food deprivation on the electroencephalogram. As a typical epileptiform manifestation, refeeding after scopolamine treatment caused a series of high-voltage polyspikes and synchronized spikes with a predominant frequency in the 1-3 Hz range. Conclusions: it was revealed that the behavioral patterns of rats and the electroencephalogram properties in these convulsions are in accordance with each other.Publication Open Access Changes in the expression of c-fos and AQP4 in the hippocampus and amygdala regions of rats with kainic acid-induced temporal lobe epilepsy and their role in the pathogenesis of disease(Galenos Yayınevi, 2022) Taşkıran, Emine; Yılmaz, Canan Uğur; Orhan, Nurcan; Kaya, Mehmet; Arıcan, Nadir; Bahçeci, Metin Berkant; Kaya, Mehmet; Gürses, Rabia Candan; Ahıshalı, Bülent; Faculty Member; Faculty Member; Faculty Member; School of Medicine; 10486; 110149; N/AObjective: aquaporin4 is the main water channel in the brain that is associated with neurological disorders. The role and the expressive changes of aquaporin4 in epilepsy are still limited and controversial. The study aims to evaluate the expression of c-fos and aquaporin4 during epileptogenesis after systemic kainic acid-induced status epilepticus in the temporal lobe epilepsy animal model and to investigate their alterations in both hippocampus and amygdala. Methods: intraperitoneal injections of kainic acid (5-15 mg/kg) by repeated low kainic acid protocol were given to young adult 32 Wistar albino rats for status epilepticus. Aquaporin4 and c-fos were investigated in the hippocampus and amygdala on days 1 and 60 after status epilepticus by immunostaining methods in brain slices. Results: the intensity of c-fos immunostaining rose considerably in the hippocampus CA1 area of rats during the acute period (P < 0.05) and in the amygdala during the chronic period. The immunostaining intensity of aquaporin4in the hippocampus of rats with acute kainic acid increased significantly (P <.05). It was also raised in the hippocampal region of the rats in the acute sham and chronic kainic acid groups. Discussion: the results of this study support a link between aquaporin4 and epilepsy. It can be speculated that aquaporin4 change is primarily a defense mechanism immediately after status epilepticus, and then, it can evolve into a causal factor with exhaustion as a result of overuse.Publication Open Access Clinical and molecular genetic findings of cerebral arteriopathy with subcortical infarcts and leukoencephalopathy(Galenos Yayınevi, 2021) Rüstemoğlu, Burcu Sevinç; Samancı, Bedia; Tepgeç, Fatih; Kürtüncü, Murat; Gündüz, Tuncay; Sayın, Gözde Yeşil; Gürvit, Hakan; Bilgiç, Başar; Toksoy, Güven; Eraksoy, Mefkure; Hanagasi, Hasmet; Uyguner, Zehra Oya; Altunoğlu, Umut; Avcı, Şahin; Faculty Member; Faculty Member; School of Medicine; Koç University Hospital; 126174; N/AObjective: most lacunar strokes are sporadic, and hypertension, diabetes, smoking, and cardiovascular diseases are among its main risk factors. Strokes caused by small vessel diseases are generally associated with single-gene disorders with familial dominant and recessive inheritance. The most common condition is cerebral autosomal dominant arteriopathy, with subcortical infarcts and leukoencephalopathy (CADASIL), associated with the NOTCH3 gene. An infrequent form of this disease is the cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), revealed with pathogenic HTRA1 gene variants related to distinct molecular pathways. The neurological and cranial magnetic resonance imaging (MRI) findings are very similar to CADASIL; however, earlier than expected onset of common alopecia in man, low back pain, and more severe memory impairment are the differences in terms of clinical presentations. Clinical findings of 22 patients from 16 families with widespread white matter lesions in the periventricular field in the brain were investigated with molecular genetic findings. Materials and Methods: clinical examination results and cranial MRI findings are reported, and NOTCH3 and HTRA1 genes are sequenced stepwise by Sanger and next-generation sequencing techniques. Results: missense changes in epidermal growth factor (EGF)-like domain in the NOTCH3 are found in 18 cases from 14 families. Two different homozygous pathogenic missense and non-sense variants, in the HTRA1 gene, were detected in four patients from two families. The disease onset age was approximately 16 years earlier in cases carrying pathogenic variants located in the encoding region of EGF-like domains 1-6 of NOTCH3. Conclusion: In the NOTCH3 gene with c.382T>C (p.C128R), c.555T>G (p.C185W), and c.1903C>T (p.R635C) and in the HTRA1 gene c.235C>T (p.Q79*) are presented for the first time in this study. Molecular genetic investigation of CADASIL and CARASIL is important to support the clinical diagnosis, determine the inheritance model, provide patient and family counseling, manage disease process, and evaluate possible treatment strategies.Publication Open Access Collaborative international research in clinical and longitudinal experience study in NMOSD(Lippincott Williams and Wilkins (LWW), 2019) Cook, Lawrence J.; Rose, John W.; Alvey, Jessica S.; Jolley, Anna Marie; Kuhn, Renee; Marron, Brie; Pederson, Melissa; Enriquez, Rene; Yearley, Jeff; McKechnie, Stephen; Han, May H.; Tomczak, Anna J.; Levy, Michael; Mealy, Maureen A.; Coleman, Jessica; Bennett, Jeffrey L.; Johnson, Ruth; Barnes-Garcia, Myka; Traboulsee, Anthony L.; Carruthers, Robert L.; Lee, Lisa Eunyoung; Schubert, Julia J.; McMullen, Katrina; Kister, Ilya; Rimler, Zoe; Reid, Allyson; Sicotte, Nancy L.; Planchon, Sarah M.; Cohen, Jeffrey A.; Ivancic, Diane; Sedlak, Jennifer L.; Sand, Ilana Katz; Repovic, Pavle; Amezcua, Lilyana; Pruitt, Ana; Amundson, Erika; Chitnis, Tanuja; Mullin, Devin S.; Klawiter, Eric C.; Russo, Andrew W.; Riley, Claire S.; Onomichi, Kaho B.; Levine, Libby; Nelson, Katherine E.; Nealon, Nancy M.; Engel, Casey; Kruse-Hoyer, Mason; Marcille, Melanie; Tornes, Leticia; Rumpf, Anne; Greer, Angela; Behne, Megan Kenneally; Rodriguez, Renee R.; Behne, Daniel W.; Blackway, Derek W.; Coords, Brian; Blaschke, Terrence F.; Sheard, Judy; Smith, Terry J.; Behne, Jacinta M.; Yeaman, Michael R.; Abboud, Hesham; Aktas, Orhan; Altintas, Ayse; Apiwattanakul, Metha; Asgari, Nasrin; Banwell, Brenda; Bichuetti, Denis; Bowen, James; Broadley, Simon; Bruck, Wolfgang; Cabre, Philippe; Cohen, Jeffrey; De Seze, Jerome; Delgado-Garcia, Guillermo; Basuroski, Irena Dujmovic; Fujihara, Kazuo; Goodman, Andrew; Havla, Joachim; Hellwig, Kerstin; Hintzen, Rogier; Hooper, D. Craig; Iorio, Raffaele; Jacob, Anu; Jarius, Sven; Jimenez Arango, Jorge Andres; John, Gareth; Kim, Ho Jin; Kim, Sung Min; Kimbrough, Dorian J.; Kissani, Najib; Kleiter, Ingo; Lana-Peixoto, Marco; Leite, M. Isabel; Liu, Yaou; Lublin, Fred; Maiga, Youssoufa; Mao-Draayer, Yang; Marignier, Romain; Matiello, Marcelo; Momtazee, Callene; Morrow, Mark; Nakashima, Ichiro; O'Connor, Kevin; Oreja-Guevara, Celia; Palace, Jacqueline; Pandit, Lekha; Paul, Friedemann; Prayoonwiwat, Naraporn; Probstel, Anne-Katrin; Qian, Peiqing; Quan, Chao; Ringelstein, Marius; Rivera, Victor; Rotstein, Dalia L.; Ruprecht, Klemens; Sa, Maria Jose; Saiz, Albert; Serguera, Che; Shosha, Eslam; Siritho, Sasitorn; Siva, Aksel; Soto de Castillo, Ibis; Stuve, Olaf; Tenembaum, Silvia; Villoslada, Pablo; Wingerchuk, Dean; Wuerfel, Jens; Yeh, E. Ann; Zamvil, Scott S.; Langer-Gould, Annette; N/A; Altıntaş, Ayşe; Faculty Member; School of Medicine; 11611Objective to develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods to illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results as of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD.
Item Metadata only Corrigendum to "Associations between sleep characteristics and glycemic variability in youth with type 1 diabetes" [Sleep Med. 109 (2023) 132-142](Elsevier B.V., 2023) 0000-0002-2614-0832; 0000-0003-3781-3892; 0000-0001-6312-6004; 0000-0002-8889-6811; 0000-0002-7855-1297; 0000-0003-3919-7763; 0000-0003-1633-9570; Boran, Perran; Barış, Hatice Ezgi; Us, Mahmut Caner; Aygün, Burcu; Haliloğlu, Belma; Bereket, Abdullah; N/A; N/A; N/A; N/A; Department of Computer Engineering; N/A; N/A; İpar, Necla; Gökçe, Tuğba; Can, Ecem; Eviz, Elif; İnan, Neslihan Gökmen; Mutlu, Rahime Gül Yeşiltepe; Hatun, Şükrü; Doctor; Doctor; Nurse; Researcher; Teaching Faculty; Faculty Member; Faculty Member; N/A; N/A; N/A; School of Medicine; College of Engineering; School of Medicine; School of Medicine; Koç University Hospital; N/A; N/A; N/A; 327618; 285581; 153511; 153504[The authors regret < that there was an error in the prevalence of T1DM in the introduction section. The correct prevalence should be 0.75/1000 in Turkey>. The authors would like to apologise for any inconvenience caused. © 2023 Elsevier B.V.Publication Open Access Cortical spreading depression can be triggered by sensory stimulation in primed wild type mouse brain: a mechanistic insight to migraine aura generation(BioMed Central, 2022) Hanalioğlu, Şahin; Sağ, Aslıhan Taşkıran; Karataş, Hülya; Demir, Buket Dönmez; Özcan, Sinem Yılmaz; Koçak, Emine Eren; Dalkara, Turgay; Özdemir, Yasemin Gürsoy; Faculty Member; Researcher; Faculty Member; School of Medicine; 170592Background: unlike the spontaneously appearing aura in migraineurs, experimentally, cortical spreading depression (CSD), the neurophysiological correlate of aura is induced by non-physiological stimuli. Consequently, neural mechanisms involved in spontaneous CSD generation, which may provide insight into how migraine starts in an otherwise healthy brain, remain largely unclear. We hypothesized that CSD can be physiologically induced by sensory stimulation in primed mouse brain. Methods: cortex was made susceptible to CSD with partial inhibition of Na+/K+-ATPase by epidural application of a low concentration of Na+/K+-ATPase blocker ouabain, allowing longer than 30-min intervals between CSDs or by knocking-down ?2 subunit of Na+/K+-ATPase, which is crucial for K+ and glutamate re-uptake, with shRNA. Stimulation-triggered CSDs and extracellular K+ changes were monitored in vivo electrophysiologically and a K+-sensitive fluoroprobe (IPG-4), respectively. Results: after priming with ouabain, photic stimulation significantly increased the CSD incidence compared with non-stimulated animals (44.0 vs. 4.9%, p < 0.001). Whisker stimulation also significantly increased the CSD incidence, albeit less effectively (14.9 vs. 2.4%, p = 0.02). Knocking-down Na+/K+-ATPase (50% decrease in mRNA) lowered the CSD threshold in all mice tested with KCl but triggered CSDs in 14.3% and 16.7% of mice with photic and whisker stimulation, respectively. Confirming Na+/K+-ATPase hypofunction, extracellular K+ significantly rose during sensory stimulation after ouabain or shRNA treatment unlike controls. In line with the higher CSD susceptibility observed, K+ rise was more prominent after ouabain. To gain insight to preventive mechanisms reducing the probability of stimulus-evoked CSDs, we applied an A1-receptor antagonist (DPCPX) to the occipital cortex, because adenosine formed during stimulation from ATP can reduce CSD susceptibility. DPCPX induced spontaneous CSDs but only small-DC shifts along with suppression of EEG spikes during photic stimulation, suggesting that the inhibition co-activated with sensory stimulation could limit CSD ignition when K+ uptake was not sufficiently suppressed as with ouabain. Conclusions: normal brain is well protected against CSD generation. For CSD to be ignited under physiological conditions, priming and predisposing factors are required as seen in migraine patients. Intense sensory stimulation has potential to trigger CSD when co-existing conditions bring extracellular K+ and glutamate concentrations over CSD-ignition threshold and stimulation-evoked inhibitory mechanisms are overcome.Publication Metadata only Expanding PRDX3 disease: broad range of onset age and infratentorial MRI signal changes(Oxford Univ Press, 2022) Rebelo, Adriana P.; Bender, Benjamin; Haack, Tobias B.; Zuchner, Stephan; Basak, A. Nazli; Synofzik, Matthis; N/A; Başak, Ayşe Nazlı; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 1512N/APublication Open Access Homozygous CAPN1 mutations causing a spastic-ataxia phenotype in 2 families(Lippincott Williams and Wilkins (LWW), 2018) Koçoğlu, Cemile; Gündoğdu, Aslı; Kocaman, Gülşen; Kahraman-Koytak, Pınar; Uluç, Kayıhan; Kızıltan, Güneş; Çağlayan, Ahmet Okay; Bilguv, Kaya; Başak, A. Nazli; Vural, Atay; Faculty Member; Koç University HospitalPublication Open Access How does entacapon affect homocysteine levels?(Galenos Yayınevi, 2021) Akdağ, Gönül; Bedir, Mithat; Çokar, Özlem; Balcı, Belgin Petek; Gül, Gülsün; Özer, Fahriye Feriha; Faculty Member; Koç University HospitalObjective: to determine homocysteine, vitamin B12, and folate levels in patients with Parkinson's disease and to investigate the effect of entacapone use on homocysteine levels. Materials and methods: the records of patients who were followed up in our outpatient clinic between 2009 and 2010 were reviewed retrospectively. The demographic, clinical characteristics, and laboratory findings of the patients were recorded. The control group consisted of healthy subjects with similar demographic characteristics. The patients were divided into two groups according to the treatment they received. Results: the control group consisted of 22 healthy subjects (group 1), group 2 comprised 22 patients [entacapone (+)], and group 3 constitued 50 patients [entacapone (-)]. The homocysteine levels of the control group were significantly lower than the entacapone (-) and entacapone (+) groups. The vitamin B12 level of the control group was significantly higher than in the entacapone (-) group. The folate levels of the control group were significantly higher than those of the entacapone (-) group. There was no significant difference between the entacapone (-) and entacapone (+) groups in terms of homocysteine, vitamin B12, and folate levels. Conclusion: levodopa treatment affects homocysteine levels in patients with Parkinson's disease. The effect of levodopa + entacapone on plasma homocysteine levels should be evaluated together with basal vitamin B12 and folate levels and genetic features. / Amaç: parkinson hastalarında homosistein, vitamin B12 ve folat düzeylerinin belirlenmesi ve entakapon kullanımının homosistein düzeylerine etkisinin araştırılması amaçlanmıştır. Gereç ve yöntem: hareket bozuklukları polikliniğimizde 2009-2010 tarihleri arasında takipli olan hastaların dosyaları retrospektif olarak incelendi. Hastaların demografik, klinik özellikleri ve laboratuvar bulguları kayıt edildi. Benzer demografik özelliklere sahip laboratuvar değerleri incelenmiş olan sağlıklı kişiler kontrol grubunu oluşturdu. Hastalar aldıkları tedaviye göre 2 gruba ayrılarak değerlendirme yapıldı. Bulgular: grup 1: Yirmi iki sağlıklı kişiden (kontrol grubu), grup 2: Yirmi iki hastadan [entakapon (+)], grup 3: Elli hastadan [entakapon (-)] oluşmaktadır. Kontrol grubunun homosistein düzeyi entakapon (-) ve entakapon (+) gruba göre anlamlı derecede düşük saptandı. Kontrol grubunun vitamin B12 düzeyi entakapon (-) grupa göre anlamlı olarak yüksek saptandı. Kontrol grubunun folat düzeyi entakapon (-) gruba göre anlamlı olarak yüksek saptandı. Entakapon (-) ve entakapon (+) gruplar arasında homosistein, vitamin B12 ve folat düzeyleri açısından anlamlı fark saptanmadı. Sonuç: Parkinson hastalarında levodopa tedavisi homosistein düzeyini etkilemektedir. Levodopa + entakapon kullanımının plazma homosistein düzeylerine etkisinin plazmanın bazal vitamin B12 ve folat düzeyleri ve genetik özelliklerle birlikte değerlendirilmesi gerektiği düşünülmüştür.